JP2006517463A - Monolayer using organic acid bonded to the surface - Google Patents

Abstract

The present invention provides a densely packed oriented organic acid-based monolayer that is chemically bonded to a substrate surface, (i) a plurality of at least one organic on at least a portion of the surface of the substrate. Providing a densely packed adsorption oriented monolayer comprising acid species, wherein each organic acid species comprising said adsorption monolayer has at least one acid functional group associated with said surface of said substrate; and ii) attaching an acid functional group associated with the surface to the surface of the substrate.

Description

Reference to Related Applications This application is filed on July 28, 2003, US Provisional Application No. 60 / 490,613, US Provisional Application No. 60 / 467,348, filed May 2, 2003, And claims priority based on US Provisional Applications Nos. 60 / 446,681 and 60 / 446,680 filed Feb. 11, 2003. All of which are incorporated herein by reference.

Providing an organic layer bonded to a substrate with background insulation, metallic properties, conductivity, or electronic properties is important for use as an interface between inorganic and organic or biomaterials in the construction of devices . Examples of bio / inorganic material interfaces include in vivo implants, such as materials for bone growth-promoting orthopedic implants, and implantable biosensors that use bioactive layers to detect chemical or biological species. In such biosensor elements, the biologically active layer (also referred to herein as a bioactive layer) is an electrical or optical proportional to the amount or concentration of species detected in conjunction with the semiconductor layer. Generate a signal. Elements using the organic / inorganic material interface are, for example, organic transistors (OT) and light emitting diodes (OLED).

  The mechanical, chemical and electronic properties between the organic or bioactive layer and the inorganic substrate depend on various factors. Many of them are: (a) the structure of the molecular part comprising the layer, eg arrangement and binding to the substrate surface; and (b) the region specific density of binding between the substrate surface and the organic layer. In addition, the interface exhibits chemical stability and must be rigid under the conditions of use or otherwise deteriorate with use.

  In general, as the region-specific density of bonds between the layer deposited on the substrate surface and the substrate increases, the stability of the layer bond increases. Furthermore, as the number of bonds between the layer and the surface at a constant surface area increases, the charge carrier flux through or away from the layer can also increase.

  It is well known to develop an organic layer covering the substrate surface using a polymerization method to deposit the polymer layer on the surface. In general, these layers do not exhibit good surface conformation. That is, the growth of the polymer overlayer is the result of surface bonding of monomer moieties at discrete locations across the surface (“islands”) (from these islands until the polymer mass eventually bridges across the surface between the islands). In the polymer as a polymerization that proceeds outward, but does not form additional chemical bonds with the surface. This growth and bonding pattern tends to form a layer that is the same thickness (often hundreds of nanometers to a few microns thick) as many layers of the species that contain the layer, but the species and substrate surface that contain the coating layer There are relatively few bonds between Also well known are organic layers comprising bulk polymers applied by, for example, the “spin-on” technique. These types of coatings also exhibit similar types of sparse bond patterns between the substrate surface and the coating. A coated substrate with a low number of bonds per unit surface area between the coating and the substrate surface has a weak mechanical bond between the substrate and the coating and low electronic communication between the substrate surface and the coating. They are therefore weak in mechanical strength and generally do not exhibit long-term stability. Such coatings do not exhibit high charge carrier properties when used in electronic devices.

  For one, since the layer is bonded to the substrate using functional groups found on the natural surface, organic layers bonded to the surface in the prior art have fewer bonds per unit surface area. In general, groups that are sufficiently active for use to bind additional species to the surface sparsely cross the surface. One example is a silanol functional group often used in derivatization reactions performed on the native oxide surface of silicon, for example, silanizing the surface with organo-chlorosilane to form a carbosiloxane species that binds to the surface. In general, the organic portion of the derivatized silane can also be incorporated into the structure of the polymer, such as unsaturated sites such as epoxides and carbon-carbon double bonds, by applying conventional organic chemistry. It contains several functional groups that are stable and stable. Alternatively, the surface can be derivatized by reduction of active surface sites to produce silane or chlorosilane species on the surface of the silicon substrate, and conventional organo-silane chemistry can be applied to form organosilane species bound to the surface. One example is the hydrosilylation of unsaturated organic moieties using surface-bonded silicon hydride functional groups prepared by such surface derivatization reactions.

  These surface derivatization methods extensively modify the starting surface and require harsh environmental control to provide moisture and oxygen sensitive substrate surfaces at the silane or chlorosilane intermediate stage during surface preparation. To do.

  As described above, the surface derivatization reaction by converting the naturally occurring active surface site to give a surface-bound layer is a multi-layer thickness and the proximity of the derivatizing species to the surface of the substrate. It provides a coating that is an area of imperfectly organized material that is an unbonded “void” area. Use of the above-described method to provide an organic layer that completely covers the surface, either by incorporation of “islands” of bound surface species or by application of bulk polymer, is poorly organized and does not adhere strongly to the surface A surface layer is provided, resulting in insufficient electronic interaction with the substrate.

  For electronic applications such as sensors, this can prevent efficient charge carrier transport through the organic layer to the substrate. For application of materials that depend on a layer bonded to the surface for adhesion and mechanical strength, for example in medical implants that promote bone growth, the discontinuous nature of the bonding of the surface layer to the substrate is It provides an interface with low mechanical strength that is easy to separate from the substrate.

  What is needed is a tissue attached to the oxide surface of the substrate with a high surface area specific number of bonds between the substrate and the substrate, despite the low number of active functional groups present on the natural surface. The organic layer. What is further needed is a general method of providing such a layer on a variety of surfaces, whether single crystal, polycrystalline, or amorphous.

SUMMARY OF THE INVENTION The inventor has surprisingly discovered that these needs are met by bonding a densely oriented monolayer containing adsorbed organic acid to the oxide surface of the substrate.

The present invention provides a step of providing a dense oriented bonded monolayer on at least a portion of a substrate surface, said step comprising:
a. Providing a substrate surface comprising a plurality of hydrolyzable functional groups;
b. At least one organic acid species having at least one acid functional group on at least a portion of the substrate surface is hydrolyzed at an interface comprising the adsorbed organic acid species and the surface of the substrate. Adsorbing in an amount sufficient to form a densely oriented monolayer comprising at least some of the acid functional groups in the vicinity of bond formation of degradable functional groups; and c. Binding at least a portion of the acid functionality to the surface hydrolyzable functionality of the substrate at the interface;
including.

  It is preferred to repeat the process of the invention until the monolayer provided by the process is substantially free of void regions and covers the entire selected portion of the oxide surface on which the monolayer is provided. .

  The “bonding” step (step c) of the present invention involves a long enough time to form a chemical bond with at least some of the acid functional groups in the interfacial region including the adsorbed monolayer and the surface functional groups, It is preferable to supply a sufficient amount of thermal energy to the interfacial region including the adsorption monolayer and the oxide surface of the substrate. More preferably, the adsorbed monolayer is bonded by heating the adsorbed monolayer and the substrate to a temperature of at least about 100 ° C.

  The adsorbing step (b) is preferably performed by supplying the organic acid species to the surface of the substrate by a method of providing the organic acid species to the surface in a form without forced long-range order. A preferred form of organic acid species is a solution comprising an organic acid species and a solvent in which the organic acid species is present at a concentration that is approximately below the critical micelle concentration of the solution.

  When the adsorption monolayer is provided from an acid solution, a preferred method of forming a densely oriented monolayer adsorbed on at least a portion of the substrate surface is a solution comprising at least one organic acid species on the surface of the substrate. And a sufficient amount to form a densely oriented monolayer. More preferably, the solution is brought into contact with the substrate surface by immersing the substrate surface in a large amount of solution.

  Preferably, after the solution contacts the substrate surface, the residual solution is removed from contact with the substrate under conditions where the adsorbed densely oriented monolayer on at least a portion of the substrate is desorbed. Preferably, by evaporating the solvent under conditions sufficient to form a densely packed oriented monolayer until the volume of the solution in which the substrate is immersed is insufficient to cover the substrate Achieved. The monomolecular layer has at least one acid functional group of a considerable number of the organic acid species in the vicinity of bond formation of the hydrolyzable functional group on the substrate surface at the interface including the adsorbed organic acid species and the surface of the substrate. It is preferable to include.

  A preferred substrate surface is an oxide surface of a substrate selected from the group consisting of a bulk oxide substrate, a metal substrate, and a semiconductor substrate. More preferred are the native oxide surface of an electronic material substrate selected from the group consisting of metals, semiconductors, and oxide conductors, and thick oxide insulator layers such as, for example, high dielectric constant glass. Particularly preferred substrates are GaAs, silicon, InP, GaN, tin oxide doped with indium and / or zinc for conduction, zinc oxide doped with aluminum for conduction, zinc oxide such as TiO, FeO and VO. A doped oxide based.

  For some applications, the organic acid species is preferably selected from the group consisting of mono-, di- and polyfunctional sulfonic acids. For most applications, the organic acid species is preferably selected from the group consisting of mono-, di- and polyfunctional carboxylic acids and mono-, di- and polyfunctional phosphonic acids. The organic acid species includes a substituted or unsubstituted thiophene moiety, a substituted or unsubstituted polythiophene moiety, and a substituted or unsubstituted hydrocarbon moiety having from about 2 to about 40 carbon atoms; the hydrocarbon moiety is optionally hydroxyl A linear or cyclic, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic substituted with a further functional group selected from the group consisting of amino, carboxylic acid, phosphonic acid and thiol functional groups It is further preferred that it comprises an organic moiety selected from the group consisting of;

  The present invention also provides densely packed, oriented organic acid based monolayers prepared by the method of the present invention.

  The above-described and other embodiments and advantages of the present invention will become apparent in the following detailed description and examples.

DETAILED DESCRIPTION OF THE INVENTION The inventor has surprisingly been able to hydrolyze crystalline, polycrystalline, or amorphous substrates by virtue of at least one functional group in substantially all portions, including monolayers. It has been discovered that a strong, along-surface, densely oriented organic monolayer bonded to a neutral surface can be provided. The inventor also surprisingly provides a monolayer that covers the surface of the substrate over selected areas of the substrate, substantially free of void areas and substantially free of areas covered by the multilayer. I found a process for this. The densely aligned organic monolayer provided by the present invention has a wide area covering the surface without void regions, a high degree of orientation of each part including the layer, and a low dimension of the layer over a large substrate area (i.e. Substantially the layer is only a single molecule thick).

  As used herein, the term “dense monolayer” includes a plurality of one or more portions bound or adsorbed onto at least a portion of a substrate surface, sufficiently broadly in a template on the surface. (I.e. whether the substrate has a crystalline, polycrystalline, or amorphous surface, the orientation of the specific substrate surface to which the coating is applied repeats according to the repetitive characteristics of the surface. Describes a membrane to provide a two-dimensional close-packed arrangement of each part that the monolayer derives). The high-density monomolecular layer is further characterized by substantially no formation of a multilayer film. As used herein, the term “oriented monolayer” means that substantially all functional groups of the molecular species forming the monolayer are in the same relative relationship with the surface and adjacent portions including the monolayer. Describe the dense monolayer bound or adsorbed on the substrate surface, present in

  The process of the present invention provides an organic layer bonded to the hydrolyzable surface of the substrate that has good mechanical and electrical properties and is resistant to desorption by solvolysis or sonication.

  The steps of the present invention are: (i) at least one acid functional group of the organic acid moiety is associated with the surface, preferably in the vicinity of bond formation, and the organic acid species are arranged on the surface in a two-dimensional regular high density packing. Adsorbing a densely oriented organic monolayer comprising a plurality of at least one organic acid species on the hydrolyzable surface of the substrate; and (ii) an acid associated with the surface of the organic acid moiety Attaching a functional group to the surface. Furthermore, the bonded monolayer is characterized in that no bilayer or multilayer is formed over any wide area of the surface.

  The inventor also surprisingly found that the densely oriented monolayer of adsorbed organic acid moieties is forced to use organic acids, also referred to herein as the “disordered state” of the acid for convenience. It has been discovered that it can be formed on a hydrolyzable surface of a substrate in a form that does not have a long-range order. Not to be bound by theory, when adsorbing to the substrate surface at the contact interface between the acid source and the surface of the substrate, the conditions under which the acid is used to provide an adsorbed monolayer according to the process of the present invention. Thus, it is considered that the film is self-assembled into an oriented monolayer film. The inventor also surprisingly selected a densely oriented monolayer of organic acid that spans a wide range of hydrolyzable surfaces, essentially free of void areas in the coating, for monolayer coating. It has been discovered that it can be provided by repeating the above-described process until a monolayer that is essentially free of voids is formed over a region of the surface of the fabricated substrate.

  The inventor has discovered that the process shown herein does not result in the formation of a coating comprising a multi-molecular layer derived from said acid species (coating species) that forms the coating of the present invention. Without being bound by theory, the coating species used to form a densely oriented adsorbed monolayer “activate” the substrate surface in the vicinity of its adsorption site during the binding step following adsorption. "it is conceivable that. Not to be bound by theory, this “activation” further leads to selective adsorption of coating species on the surface in close proximity to the portion of the surface that supports the bound monolayer coating during subsequent processing cycles, As a result, it is believed to provide a monolayer coating over a larger area of the substrate than the multi-layer formation found in other coating methods.

  As mentioned herein and without needing to be bound by theory, the coating process of the present invention is intended to provide the coating of the present invention on all hydrolyzable surfaces and in particular on oxide-containing surfaces. It is thought that it is applicable to. The present invention is described with respect to oxide-containing surfaces and is exemplified below, but the same principles apply to surfaces containing species other than oxides activated by the same proton transfer process as described below. It will be understood that it is possible. Thus, for example, bare silicon nitride surfaces are known to hydrolyze to form a protective oxide coating when exposed to an atmospheric environment. Such oxide coatings provide a hydrolyzable surface to which a coating of the present invention derived from an organic acid can be applied according to the principles described herein. Also, bare silicon nitride surface is the same before being hydrolyzed by atmospheric humidity if the surface is protected from humidity during the coating process so that the surface does not hydrolyze first to become an oxide surface. It will be understood that the present invention provides a hydrolyzable surface to which the coating of the present invention can be applied. It is contemplated that other non-oxide surfaces that can be subject to hydrolysis by acid species that induce coatings can also be provided with monolayer coatings that include organic acid moieties in accordance with the principles of the invention described herein. Will be done.

  The following is a process for preparing a high density monolayer bonded to the oxide surface of the substrate, a suitable organic acid used to provide the monolayer of the present invention, and a high density, oriented, surface bonded of the present invention. A substrate having or that can be made to have an oxide surface suitable for use in the preparation of a substrate having an organic acid-based monolayer is described.

  As used herein with reference to an adsorbing layer, the term densely oriented monolayer is a monomolecule whose arrangement approaches a close packed two-dimensional “crystal-like” arrangement of species adsorbed on the surface. Contains an array of individual acid species including layers.

  Monolayers with this type of packing are, for example, octadecylphosphonic acid adsorbed on mica substrates as described by Neves et al. In Langmuir 2001, 17, pp 8193-8198, which is incorporated herein by reference in its entirety. It was observed on a very regular surface with few defects. Neves et al. Contacted a mica surface with a low concentration solution of an organic acid (octadecylphosphonic acid) to create a sparse coating of the surface, that is, an “island” of monolayer coating in which large “voids” are scattered in the surface coating It was observed that the acid species was adsorbed on the surface in the form of a monolayer region of acid organized, although on the containing surface. Neves et al. Have not identified conditions when contact with a low concentration solution of organic acid on the mica surface provides a monolayer that covers substantially all of the macroscopic area of the surface. Neves et al. Also contact the mica surface with a sufficiently concentrated octadecylphosphonic acid solution to first deposit domains containing multi-layers of phosphonic acid in widely dispersed regions ("islands") on the mica surface. Was observed. After removing the surplus solution from the surface of the mica substrate (surface with high regularity and low defects for the specific acid studied), Neves et al. The layers redistributed over time, interspersed with void areas that were not covered, but were observed over time to form dense monolayer regions with a two-dimensional crystal-like structure. Neves et al. Have not observed that these monomolecular layers are enlarged and do not substantially contain voids, and at the same time do not deposit a multi-molecular layer on a portion of the surface, covering the entire surface. . Neves et al. Further observed that applying this method to other substrates gives only multi-layer islands. Thus, the native oxide surface of glass, silicon or gallium arsenide provides only an unstructured multi-layered adsorption film.

  Two-dimensional arrays of molecular species are described in, for example, K.K. Brodgett, Journal of the American Chemical Society, 1935 (vol. 57) pp. A first over a denser, immiscible second liquid species that forms a one-dimensional dimensional organized film on the surface of the denser liquid, as described in 1007-1022. It is also found in classically formed Langmuir-Blodgett monolayers that require the application of two dimensional forces sufficient to form an ordered layer on the liquid species.

  As noted above, prior art for providing a monolayer organized on a substrate surface, such as provided in the formation of Langmuir-Blodgett films, without forced long-range organization. The process is limited to sparse coatings of highly regular surfaces with few defects and monolayer species.

  The inventor has developed a densely oriented organic monolayer comprising an organic acid moiety, such as a phosphonic acid moiety, substantially free of void areas and covering a macroscopic area of the substrate surface: (i) Forming, at least in part, an adsorbed, densely oriented monolayer comprising an organic acid species, and (ii) binding the species comprising the monolayer to the substrate surface. It has been discovered that it can be formed by iterating until a monolayer bonded to the surface is formed that covers the desired area of the substrate without being included.

Process The present invention provides (a) a substrate having a surface containing excess hydrolyzable functional groups; (b) adsorbing a densely aligned monolayer film comprising a plurality of at least one organic acid species on the substrate surface And wherein the thin film is further oriented so that at least one acid functional group of a plurality of organic acid species including a monomolecular layer associates with a hydrolyzable functional group on the substrate surface; c) providing conditions necessary to bind the majority of the acid functional groups associated with the surface of the organic acid moiety comprising the adsorbed monolayer to the hydrolyzable functional group comprising the substrate surface; A monolayer coating bonded to a substrate surface is provided that includes a portion derived from one organic acid species. Further, the process of the present invention provides for a region of the substrate in which substantially the entire selected portion of the substrate is substantially free of regions of the substrate that are covered with the multilayer and substantially lacks monolayer coverage. May be repeated until covered by a monolayer attached to the substrate. For most applications, continuous cycles of the process can be performed continuously at high speed, and continuous coating operations can be performed remotely in time and / or location, but are within the scope of the present invention. Will be understood. It is also understood that the various process steps described above can in principle be performed simultaneously, remotely in time and / or location, or at the same location and separated in time and are within the scope of the present invention. It will be.

  The process of the present invention is described and exemplified below using a substrate surface comprising a hydrolyzable functional group comprising an oxide, and preferably the hydrolyzable functional group on the substrate surface being an oxide functional group, It will be understood that the above steps can be performed on substrates containing other hydrolyzable functional groups and are within the scope of the present invention.

Providing a densely oriented adsorbed monolayer An essential step in providing a densely oriented monolayer bonded to the substrate surface is to adsorb the adsorbed monolayer of the organic acid species on which the bonded monolayer is formed. To provide at least a portion. The adsorbed monolayer is further characterized by having a high density oriented array of organic acid species. Preferably, the organic acid species has an acid functional group associated with the substrate. It will be understood that any method can be used to provide a densely oriented monolayer with adsorbed organic acid species (also referred to herein as a “dense monolayer” for convenience). These terms are as defined above.

  Methods for forming a preferred adsorption monolayer from the standpoint of convenience and scalability include: (i) contacting the surface of a portion of the substrate to be coated with a low concentration solution of an organic acid species on which the adsorption monolayer is formed; (Ii) following step (i), removing the residual solution from contact with the substrate surface under conditions where the densely oriented organic monolayer on at least a portion of the substrate surface is detached; and (iii) And) removing substantially all of the solvent associated with the adsorbed organic acid monolayer after removal of the residual solution or simultaneously with removal of the residual solution from the monolayer.

  One method for performing step (i) of this deposition procedure is to immerse the surface in an acid solution having a low acid concentration, as described below. One method of immersing the surface is by immersing the substrate on which the monolayer is deposited or a portion of the surface in a bulk solution of acid (dip coating). Another way to immerse the surface is to dispense a large amount of acid solution onto the surface in an amount that exceeds what is normally required to wet the surface to which the monolayer adsorbs or a portion of the substrate surface. coating). It will be appreciated that other methods such as spraying, fogging, spin coating, etc. can also be used to immerse the substrate surface in the acid solution.

  Typically, immediately after contacting the substrate surface with an organic acid solution, the rest of the solution in contact with the surface is removed from contact with the surface under conditions where the densely oriented adsorption monolayer is desorbed. The process begins. As described in detail below, it is important to remove the solution from contact with the surface under conditions where the densely oriented monolayer of acid species adsorbed on at least a portion of the surface is desorbed.

  In step (i) of the “dip coating” process, the surface of the substrate on which the adsorption monolayer of acid species is applied is placed under the liquid surface of a large amount of acid solution (bulk solution). It can be simply performed by suspending so as to be arranged perpendicularly to a plane (meniscus plane) including the plane. Step (ii) of the “dip coating” process (removing the residual solution from contact with the substrate under conditions where the densely oriented organic monolayer on at least a portion of the substrate surface is desorbed) The bulk solution solvent can be simply evaporated by evaporating the bulk solution solvent so that the meniscus on the surface of the bulk solution to be evaporated crosses the substrate surface in the region where the adsorption monolayer is applied.

  In general, the evaporation is preferably performed for 24 hours or less, preferably about 4 hours or less after the substrate is suspended in the bulk solution. However, longer or shorter times can be used depending on the concentration of organic acid in the solution and the acid affinity of the substrate surface to be coated. When this coating method is used, it is preferable to use a bulk solution having a low acid concentration, as will be described in detail below. Particularly preferably, for the particular acid and solvent used, during application of the adsorbed monolayer after evaporation of the bulk solvent, the acid in the residual solution will also be at a concentration below the critical micelle concentration or saturation concentration of the acid. In addition, the acid concentration is sufficiently lower than the critical micelle concentration or saturation concentration (discussed below).

  Stage (i) of the “drop coating” process, where the surface is immersed in an acid solution, places the substrate surface on which the coating is applied horizontally, and the solution “stores” on that portion of the surface where the acid monolayer adsorbs. As such, a measured amount of acid solution is dispensed onto the surface. If a drop coating process is used, process step (ii) (residual solution is removed from contact with the substrate under conditions where the densely oriented organic monolayer on at least a portion of the substrate surface is detached) ) Directs a gas stream, for example nitrogen, across the substrate surface to the region where the monolayer of organic acid is adsorbed, resulting in a gas / solution interface across the surface that gradually flushes residual solution off the surface Thus, it can be conveniently achieved by flowing a gas flow over the surface.

  The use of either of these two methods to remove excess coating solution from contact with the substrate surface also includes step (iii), essentially simultaneously with removal of excess solution from contact with the substrate surface, It will be appreciated that evaporation of substantially all of the solvent associated with the adsorbed monolayer is also achieved. For example: (i) flooding the surface with excess organic acid solution; (ii) removing excess solution from contact with the surface by increasing the rotational speed of the substrate and mechanically shaking away the excess solution; and (iii) It is believed that other methods such as spin-coating processes, which include stripping the solvent with a gas stream directed toward the rotating surface, can also be used to apply densely aligned monolayers adsorbed with organic acid species. I will. Other coating methods are known to those skilled in the art.

  The inventor has found that a simple bulk solution dip coating that does not remove excess solution remaining on the surface in accordance with the principles described herein, or a simple drop solution and subsequent “reserved” solution from the substrate surface. It has been observed that such evaporation generally does not result in the formation of a densely oriented, adsorbed organic acid species monolayer on the substrate surface. Thus, attempts to provide an organic layer bonded to the substrate surface by providing an adsorbed acid layer using an acid solution without removing the solution from contact with the surface according to the principles described below are non-regular. The result is simply an organic multilayer.

  One property common to the above-described methods for removing residual acid solution from contact with the surface is that these methods divide a portion of the substrate surface on which the acid adsorption monolayer is provided with the substrate surface and the acid. A method of crossing the adsorbed monomolecular layer at the interface including the surface of the acid solution to be deposited. Needless to say, it is considered that when the acid solution contacts the surface according to the above-described principle, an interface is formed at the contact point between the substrate surface and the acid solution surface. As mentioned above, an example of such an interface is the contact between the substrate surface and the surface of the bulk solution as it evaporates. Another example of such an interface is a contact at the edge of a “reserved” solution present on a horizontally disposed substrate surface. Furthermore, it goes without saying again that the acid species dissolved in the solution at the interface between the surface of the solution and the substrate surface are oriented aggregates from which the densely oriented monolayer of the present invention is deposited. It is thought to be self-organizing. Thus, the step of using an acid solution to provide an adsorbed monolayer on the substrate surface causes the substrate surface to be a substrate surface / solution surface so that the acid self-assembles and forms an acid monolayer on the surface. It will be appreciated that any process for removing the remaining solution from the substrate surface by slowly traversing at the interface can be used. Deposition of densely adsorbed monolayers using such a slow traversal of the substrate surface at the contact point between the surface of the acid solution and the substrate surface is conveniently referred to herein as an acid solution meniscus. Is also expressed as crossing the substrate surface.

  The inventor has discovered that with the simple “dip” coating described above, typically a single deposition operation provides a coating with about 90% densely oriented monolayer of the surface. did. The coated surface area can be increased by combining the adsorbed monolayer provided in a single operation and by repeating the “dip” coating operation on the substrate. Such a dip coating and bonding cycle can be repeated until substantially the entire surface is covered with an organic monolayer. In some cases, a high degree of coating can be obtained with a single application by increasing the concentration of the acid species. For example, as described herein, if it is impractical due to solution agglomeration or solubility problems, or the surface is attacked by acid species or high concentrations of acid species, If only weakly adsorbed, the inventor has found that repeated cycles of “dip” coating operations can use acid species at very low concentrations to provide a substantially complete monolayer surface coating over a large surface area. did.

  In order to demonstrate the improved surface coverage of the coating provided in accordance with the present invention, a monolayer film prepared by the prior art is examined using surface probe microscopy techniques such as atomic force microscopy. The complete coating of the surface, ie the surface coating that does not include the region lacking the coating film, has a size on the order of nanometers. The inventor surprisingly found that in films prepared by the process of the present invention, several dozen organic monolayer films could be found even to find pinhole defects to measure the thickness of the bonded monolayer. I found that I had to look over the micron range.

  As noted above, when solution methods are used to provide a densely oriented adsorption organic monolayer, solutions having an acid concentration of “low” or “below critical micelle concentration” are preferably used. The term “critical micelle concentration” is described by Kozo Shinoda in Solvent Properties of Surfactant Solutions, (1967), Marcel Dekker, Inc. N. Y. , Part 2, chapter 3, “Solvent Properties of Nonionic Surfactants in Aqueous Solutions”, page 42. Have been discussed. The critical micelle concentration (CMC) of a species in solution represents a concentration level sufficient for the dissolved species to form a micelle structure. Thus, at concentrations below CMC, dissolved species exist as unimolecular species surrounded by a solvent “shell”, and at concentrations above CMC, dissolved species aggregate into micelle “domains” in solution. As observed by Neves et al., As discussed above, contact of the surface with an agglomerated structure, ie, a solution containing micelles and bilayers, gives a multilayer of dissolved material in contact with the surface. . Therefore, in the process of the present invention using an acid solution to provide an adsorption monolayer, it is preferable to use a solution having an acid concentration lower than the critical micelle concentration.

  Depending on the combination of acid and solvent, the acid may be too poorly soluble in the solvent to provide a solution of sufficient concentration to reach the point where a structure such as a bilayer begins to form in the solution. Will be understood. As is known, when the concentration of dissolved seeds exceeds the saturation point of the solution, the seeds begin to precipitate in crystalline form. Therefore, from the standpoint of convenience, it is understood that when an acid species and solvent having low solubility are used in the process of the present invention, it is preferable to use an acid solution having a concentration of acid species lower than the saturation point of the solute. I will. Thus, as used herein, the term "low concentration" of acid is lower than a saturated solution of acid in the solvent used, suitable for the particular acid and solvent, in view of the discussion above. Or a concentration lower than the critical micelle concentration of the acid solution. As will be described in detail below, it is preferable to select a solvent having low acid solubility for the purpose of providing an oriented high-density organic monolayer adsorbed according to the solution method according to an embodiment of the present invention.

  In the solution method for providing the adsorption monolayer on the substrate surface, the solubility of the acid species in the solution must also be taken into account. In general, it is preferable to use a solvent in which the acid species including the monomolecular layer has a lower affinity for the surface. Therefore, any solvent that has a high solubility of the acid species and can elute the acid-adsorbed monolayer from the substrate surface is not preferred. Not to be bound by theory, the choice of a solvent in which the acid species is almost insoluble or poorly soluble can be determined by high density orientation, such as when the solution method as described above is used, as these terms are used in the practice. Helps provide an adsorption monolayer to the substrate surface. In contact of the substrate surface with a solution containing an acid species and a solvent with low solubility of the acid species, the affinity of the acid to the surface drives the acid to self-assemble into a densely oriented adsorption monolayer on the substrate surface. It is thought that it can provide power.

  In accordance with the principle governing the adsorption affinity of certain acid species to the substrate surface, solvents with high acid solubility, and acid concentrations exceeding those indicated above as preferred, are also highly oriented single molecules adsorbed on the substrate surface. It will be understood that it can be used to deposit layers. Not to be bound by theory, concentration and / or solvent conditions that deviate from the above can be attributed to the interaction between the organic acid species and the substrate surface on which the acid adsorption monolayer is deposited, and the deposition of organic acid species aggregates. If it is sufficiently energetically advantageous to facilitate the deposition of monolayers of acid species and / or if the species between which the equilibrium between the deposited and dissolved species is deposited is advantageous It can be used. Thus, any acid species adsorbed during the deposition process is disadvantageous to redissolve in the solution and / or aggregate deposition on the surface is disadvantageous and / or any adsorbed to the surface Conditions that favor the redistribution of acid aggregates into monolayers allow use of conditions that deviate from the above preferred conditions and are within the scope of the process of the present invention.

Bonding of adsorbed monolayer with substrate In the process of the present invention, after providing a high-density oriented adsorbed monolayer containing an organic acid on the surface of the substrate, remote from the provision of the adsorbed monolayer or in time In the bonding step, which can be simultaneous with the formation of the layer, the layer is bonded to the substrate surface. The bonding step provides a monomolecular layer chemically bonded to the substrate surface in the region where the monomolecular layer is adsorbed.

  Not to be bound by theory, when the substrate surface is an oxide, the generation of water from the interface between the acid functional group associated with the surface of the organic acid species including the adsorption monolayer and the oxide surface of the substrate is It is considered essential to form a bond between the adsorbed organic acid species and the oxide surface of the substrate. Thus, one method for providing the conditions necessary to form a bond between an organic acid species containing an adsorbed monolayer and a substrate surface is by heating the substrate and the adsorbed monolayer. Conveniently, the substrate and the adsorbed monolayer for a time sufficient to form a bond with the oxide surface of the substrate in substantially all acid species including the adsorbed monolayer in an oven at a temperature in excess of 100 ° C. It can be achieved by installing. It will be appreciated that other methods of supplying sufficient energy in the interfacial region including the adsorbed monolayer and the substrate surface may be used, such as radiant heating and microwave irradiation.

  It will be understood that the formation of a combined organic acid species-based monolayer does not depend on the surface area density of water physisorbed and chemisorbed on the native oxide substrate. Indeed, one advantage of the process of the present invention and the monolayer provided thereby is that the surface area bonded per unit surface area, also referred to herein as surface bond species density, for convenience herein, is the surface area of the monolayer. The number of moles of species is not related to the density of normal active species on the natural surface of the substrate. This embodiment of the invention allows a monolayer that is essentially free of voids to be applied to selected areas of the substrate surface. Complete coverage of the macroscopic area of the substrate surface with an organic acid-based bonded monolayer can be achieved by repeating the steps of the process described above. That is, providing a densely oriented monolayer with adsorbed organic acid species until complete monolayer coverage is achieved, and then between the organic acid species containing the adsorbed monolayer and the oxide surface of the substrate. Forming a bond.

  As described above, a substrate having a surface other than an oxide is also applied when the substrate surface contains excess functional groups that can be hydrolyzed by an organic acid, and when the surface is coated with a high-density oriented adsorption monolayer containing an organic acid. Organic monolayer coatings can be provided in accordance with the present invention. An example of such a surface is a bare silicon nitride ceramic surface as described above. Other substrate surfaces are known to those skilled in the art.

Providing an organic acid-based monolayer bonded to the native oxide surface of an organic acid substrate requires the use of organic acid species in the process described above. As used herein, the term organic acid species is at least one selected from phosphonic acid (—PO ₃ H ₂ ), carboxylic acid (—CO ₂ H), and sulfonic acid (—SO ₃ H). Includes molecules having acid functional groups as well as moieties containing organic moieties attached thereto. Most preferably, the organic acid contains phosphonic acid and carboxylic acid functional groups, and the organic acid contains phosphonic acid. The organic acid moiety attached to the acid functional group may be substituted with one or more additional functional groups selected from the group consisting of hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, amino, alkyl, ether, and thiol functional groups. .

  Generally, the acid used to provide the organic layer according to the present invention preferably contains an organic moiety containing about 2 to about 40 carbon atoms, more preferably an organic moiety containing about 2 to about 20 carbon atoms. . More preferably, the acid comprises an organic moiety that has been treated to add to a close packed arrangement when the acid is adsorbed to the substrate surface.

  Organic moieties such that when a difunctional or polyfunctional moiety is used, at least one of the functional groups is in a di-terminal relationship with the functional group having the strongest affinity for the surface It will be appreciated that it is preferable to have the treated functional group above. As described above, when the monomolecular layer including a plurality of organic acid species is adsorbed on the substrate surface having one acid functional group associated with the substrate surface, the second acid functional group is directed away from the substrate surface. Thus, the second acid group becomes accessible and participates in further chemical reactions.

  Suitable organic moieties are selected from aromatic, heteroaromatic, and aliphatic moieties including saturated and unsaturated alkyl moieties. In addition, the organic moiety may be substituted with additional aliphatic or aromatic moieties and one or more functional groups. The aliphatic moiety may be linear, branched, or cyclic, saturated or unsaturated. Aromatic moieties may include polymeric compounds such as oligomeric compounds such as biphenyl, for example linear phenylenes such as sexiphenylene, polycyclic fused aromatic ring systems such as pentacene and anthracene and heterocyclic analogs thereof. . Heteroaromatic moieties may include monomeric moieties such as, for example, pyrrole and thiophene, and oligomeric and polymeric heterocyclic moieties such as, for example, oligothiophene, such as quarterthiophene and sexithiophene.

  Preferred organic moieties include linear or branched alkyl moieties having from about 2 to about 40 carbon atoms, and further include hydroxyl, amino, carboxylic acid, carboxylate, phosphonic acid, phosphonate It may be substituted with one or more functional groups selected from the group consisting of functional groups, ether functional groups, and thiol functional groups (thus bifunctional or polyfunctional in which the organic monolayer of the present invention is prepared) Provide acid). Also preferred are organic moieties selected from the group consisting of substituted and unsubstituted pentacene, substituted and unsubstituted anthracene, and substituted and unsubstituted thiophene and polythiophene, and substituted and unsubstituted xylene.

  More preferred are organic moieties based on derivatives of TCNQ and TTF known as electron acceptor and donor molecules, the structure of which is represented below as Structure I. As is known, TCNQ and TTF are typically used as substructures for providing organic conductors.

  Molecular derivatives of TCNQ with altered electron acceptor properties are known, for example, Yamashita et al., Et al., Which is hereby incorporated by reference in its entirety. Journal of Materials: Chemistry, (1998), 8 (9), pages 1933-1944. These known TCNQs include substitution of electron withdrawing substituents such as, for example, chlorine and fluorine (with respect to structure I, the structural position is represented by “e”) to improve the properties as an electron acceptor. . Further alternatively or in addition, it is known that TCNQ can further improve its electron accepting properties by substituting the positions occupied by cyano groups with electron withdrawing groups.

  Also known are TTF derivative compounds with altered electron donating properties. Such molecules are described, for example, in Hasegawa et al., Which is incorporated herein by reference in its entirety. , Synthetic Metals (1997), 86, pages 1801-1802. As described, TTF can also be substituted with respect to structure I for the position represented by “e” with an electron donating group to improve its electron donating properties.

  In accordance with these well-known principles and as described above, other groups of acid moieties containing organic acids used in the preparation of the organic layers of the present invention are TCNQ or TTF molecules or one or more derivatives thereof. It contains an organic moiety based on An example is shown in Structure II. Structure II includes a phosphonic acid containing an organic moiety (shown in parentheses) based on the TCNQ derivative structure.

  The above phosphonic acid derivative contains the TCNQ basic structure, and the pyridylphosphonic acid functional group replaces one of the cyano groups of the TCNQ parent compound. As will be appreciated, and in accordance with the discussion above, the derivative may have an electron withdrawing group that replaces one to all of the positions represented by “e” in the structure of structure II. It will further be appreciated that any remaining cyano group of the phosphonic acid of structural formula II may be further or alternatively substituted with an electron withdrawing group. It will also be appreciated that the phosphonic acid described above may be substituted with other acids and additional acid groups may be added to the phosphonic acid of structure II. For example, a diphosphonic acid derivative of TCNQ is described in Katz, H., et al., Which is incorporated herein by reference in its entirety. E. , And Schilling, M .; L. , Journal of Organic Chemistry, (1991) 56, pages 5318-5324. In the Katz bisphosphonic acid molecule (with respect to structure II above), the cyano group indicated by an asterisk (as shown in structure II, the upper right cyano group) is substituted with a second pyridylphosphonic acid functional group and is symmetrical. Bisphosphonic acid is provided. It will be appreciated that many other variations and modifications are possible in which the organic monolayers of the present invention can be prepared.

  Similarly, the addition of an acid functional group such as pyridylphosphonic acid to one or more of the positions represented by “e” of the TTF structure shown in Structure I provides useful electron donating properties for the preparation of the coatings of the present invention. It will be apparent that an organic acid is provided. Thus, it will be understood that a film having a mixture of the two species can also be prepared that has similar conductivity to the organic conductors prepared from TCNQ and TTF parent compounds. Other organic acid derivatives of both TCNQ and TTF parent compounds are known to those skilled in the art.

  Preferably, the phosphonic acid is nitrophenyl phosphonic acid, benzyl phosphonic acid, butyl phosphonic acid, octyl phosphonic acid, dodecyl phosphonic acid, octadecyl phosphonic acid, substituted and unsubstituted anthracene phosphonic acid, substituted and unsubstituted pentacene phosphonic acid. Acids, substituted and unsubstituted quarterthiophenephosphonic acids, 11-hydroxyundecylphosphonic acids, substituted and unsubstituted xylylphosphonic acids, omega-substituted phosphonic acids having a hydrocarbon moiety containing from about 2 to about 20 carbon atoms The omega substituents are each independently selected from the group consisting of carboxylic acid, hydroxyl, amino, phosphonic acid, ether, polyether, and thiol functional groups; and selected from the group consisting of two or more of these acids It is a combination.

  Further preferably, the carboxylic acid is selected from the group consisting of alkyl carboxylic acids having about 2 to about 40 carbon atoms, salicylic acid, and substituted and unsubstituted alkyl salicylic acid, benzoic acid, and substituted benzoic acid, Linear or branched, wherein the group may be substituted with one or more functional groups selected from the group consisting of hydroxyl functional groups, amino functional groups, carboxylic acid functional groups, and hydroxyl, amino, carboxylic acid functional groups, Including at least one selected from the group consisting of substituted or unsubstituted alkyl moieties having from about 2 to about 20 carbon atoms.

  It will also be understood that the mixture of two or more organic acid species described above can be used in the process of the present invention to the extent that they are compatible in view of the affinity for the substrate and the packing arrangement.

Substrate Surface As described herein, the present invention is a method of bonding a monolayer comprising a plurality of organic acid species to a substrate surface. Suitable substrates are metallic, conductive, semiconducting, and insulating (these terms are, for example, West, Basic Solid State Chemistry, second edition, John Wiley & Sons, New, which is incorporated herein by reference in its entirety. York, pp. 110-120). Examples of substrates suitable for use in the process of the present invention include, but are not limited to, materials having a native oxide surface, i.e., containing oxides or exposed to atmospheric environments to form native oxides. . Non-limiting examples of oxide materials include bulk metal oxides such as silica and alumina, conductive oxides such as indium doped tin oxide and zinc / indium doped tin oxide, and integrated circuit An oxide insulator such as a low dielectric constant glass of a gate insulating material can be given. Non-limiting examples of materials that form natural metal oxide surfaces when exposed to the atmosphere, such as depositing oxide coatings that are exposed to the atmosphere and not ablated, such as titanium, titanium alloys, aluminum, and aluminum alloys Metal to be used. Further examples of materials that are exposed to the atmosphere to deposit a native oxide layer include ceramic materials such as silicon nitride and semiconductors such as silicon. Also suitable for application of the coating of the present invention is a material having a deliberately provided oxide coating, such as a thick film oxide insulator of a semiconductor device, as well as, for example, gallium arsenide, gallium nitride, and carbonized It can be derived from an oxide surface such as silicon. Also suitable for use in providing the bound monolayer of the present invention is subject to hydrolysis and has an adsorptive affinity for carboxylic acid or phosphonic acid functional groups, and thus as described above, the process of the present invention. Although it is not particularly limited, it is a bare surface such as silicon nitride.

  Particularly preferred substrates are those useful for the preparation of electronic or mechanical elements for contacting living tissue or fluids. One example of a substrate useful for the preparation of electronic devices is a thick oxide insulating layer on a gate junction used in bioelectronic sensors suitable for in vitro and in vivo diagnostics and condition monitoring. An example of a surface useful for the preparation of a mechanical element is a graft material such as a titanium reinforcement useful for bone tissue repair in vivo.

As described above, suitable surfaces include the surface of a semiconductor substrate such as a silicon single crystal surface. Suitable surfaces also include, for example, metals such as titanium and its alloys, aluminum and its alloys, and the surfaces of polycrystalline substrates such as silicon. Also included is the surface of an amorphous substrate, such as the surface of an oxide conductor or oxide insulator. Examples of oxide conductors include Fe ₃ O ₄ , tin oxide doped with indium and / or zinc for electrical conductivity, zinc oxide doped with aluminum for electrical conductivity, zinc oxide, and semi-metals such as TiO and VO. Stoichiometric oxides are mentioned.

  Also preferred are ceramic substrates such as silicon nitride and silicon carbide, and semiconductors such as germanium and semiconducting germanium based compounds.

  When an oxide substrate surface is used, the oxide surface is generally cleaned by washing the surface to remove residual metals and organics, and typically by rinsing with water after the oxidation treatment, thereby removing the monolayer. You have to prepare for the position. For a surface that is stable to such processing, such as a monocrystalline or polycrystalline silicon wafer surface, a method typically used to clean a silicon wafer prior to microfabrication of an integrated circuit on the wafer, The surface can be treated with a standard hydrogen peroxide / sulfuric acid “piranha” solution, then rinsed with water, and a second treatment with a standard hydrogen peroxide / hydrochloric acid “buzzard” solution. In general, the process of the present invention gives the best results on oxide surfaces that are free of base species, zero valent metals, and residual hydrocarbon species. However, even on surfaces that cannot be subjected to standard rigorous cleaning of semiconductors, such as oxide conductors, the process of the present invention still provides a monolayer that exhibits good surface conformation with the oxide surface of the substrate. Other cleaning methods that are applicable to specific surfaces to remove unwanted species typical of these surfaces are known to those skilled in the art.

EXAMPLES The present invention is broadly applicable to hydrolyzable surfaces, but the following examples are doped with monolayers of phosphonic acid or carboxylic acid based organic layers, single crystal silicon substrates, titanium alloy substrates, and indium. The deposition on the oxide surface of a tin oxide substrate is shown. The examples are intended to illustrate the process of the present invention and the film formed thereby, and are not intended to limit the scope of the present invention. It will be appreciated that many modifications can be made to the materials and process steps exemplified below and still be within the scope of the process and membranes of the present invention.

Example 1. Deposition of phosphonic acid onto a silicon substrate In all of the examples using a silicon substrate, the substrate was prepared as follows. Single-crystal silicon (100) polished 12 inch wafers (University Wafer inventory) were cut into square coupons by slitting and breaking. The coupon has a thickness of about 0.55 mm (wafer thickness) and has two sets of approximately 8 mm long sides each in parallel, and thus two 64 mm ² square faces. First, a coupon is made with a sulfuric acid / hydrogen peroxide solution (concentrated (95 to 97%) H ₂ SO ₄ aqueous solution: 30% H ₂ O ₂ is 1: 3 v / v, also referred to as a piranha solution for convenience in this specification). Boiled for 15 minutes to remove some metal and organics from the coupon. After treatment with the piranha solution, the coupon was rinsed with running deionized water about 6-7 times. The total volume of the rinsed water combined was about 140 ml. After rinsing, the coupon is boiled for about 15 minutes with a hydrochloric acid / hydrogen peroxide solution (32% aqueous HCl: 30% H ₂ O ₂ is 1: 1 v / v, also referred to herein as a “buzzard” solution for convenience). did. After treatment with the buzz solution, the coupon was rinsed about 6-7 times with a stream of 18.2 megohm deionized water (total volume about 1 liter) and dried under a vacuum of about 10 mTorr for at least 24 hours.

In all of the examples, the deposition of a phosphonic acid-based monolayer on the oxide surface of a silicon substrate causes the monolayer containing the selected phosphonic acid to be adsorbed on the 0.5 cm ² face of the substrate, The substrate and adsorbed monolayer were then heated to form a bond between the oxide functional group containing the substrate surface and the phosphonic acid species containing the adsorbed monolayer.

In all examples, the following procedure was used to apply an adsorbed phosphonic acid-based monolayer to the substrate surface. To suspend a substrate in a phosphonic acid solution in which a coupon for a silicon substrate prepared as described above is placed in a beaker having a narrow diameter (a tall beaker, in which the acid solution becomes a relatively long column with a certain volume of acid solution). It was installed in the holder designed. The coupon is soaked in the acid solution and the holder is placed so that the two sides of the coupon and the 64 mm ² surface are oriented substantially perpendicular to the surface containing the surface meniscus of the phosphonic acid solution (meniscus surface). A solution of the selected phosphonic acid was prepared by dissolving the weighed acid in tetrahydrofuran (THF, commercial product, technical grade solvent, distilled from sodium benzophenone before use) at the following concentrations at room temperature.

  About 40 ml of phosphonic acid solution was placed in a 50 ml tall beaker. Using the holder, the substrate was suspended in a beaker so that the uppermost side of the substrate was immersed below the meniscus surface of the solution. Immediately after the coupon is immersed in the solution, the solvent is evaporated from the beaker to reduce the volume of the solution so that the meniscus of the phosphonic acid solution crosses the surface of the suspended coupon (substrate surface) as the solvent evaporates. . Evaporation was performed under atmospheric conditions until the meniscus surface of the residual solution was below the lower end of the coupon. As described above, the amount of solvent required to evaporate and cross the coupon surface across the meniscus of the acid solution is minimized, and thus the beaker's adsorption during the deposition of the phosphonic acid adsorption monolayer on the substrate surface. A tall beaker was selected as the bulk solvent container to minimize the concentration change of the acid solution therein. The amount of acid used to prepare the solution was chosen so that, even after the evaporation step, the remaining bulk acid solution had an acid concentration below the saturation concentration of the solution. For example, in the case of deposition of 11-hydroxyundecylphosphonic acid, an initial concentration 0.1 mM THF solution was prepared. After evaporation, the residual solution has a 33% increase in concentration, which is lower than the saturated concentration of the acid in THF estimated at room temperature, from about 25 mM to about 50 mM.

  A number of silicon coupons with adsorbed phosphonic acid monolayers were prepared according to the procedure described above. Table I shows the acid used to prepare the adsorbed monolayer and the acid concentration in the solution at each deposition.

  After the acid adsorption monolayer was adsorbed to the substrate, each coupon was placed in a convection oven operating at about 130 ° C. and heated for about 48 hours. After 48 hours, the coupon was removed from the oven and cooled to room temperature in the atmosphere. The coupon was then processed according to the following procedure to remove the adsorbed or aggregated material in the ultrasonic bath (Branson) by ultrasonic cleaning.

  An organic monolayer based on 11-hydroxyundecylphosphonic acid was ultrasonically washed in a triethylamine / ethanol solution heated to about 50 ° C. for about 30 minutes. Coupons prepared with other monolayer species are about 20 minutes at room temperature in 0.5 M potassium carbonate solution (2: 1 v / v ethanol / water, also referred to herein as “carbonated rinse solution” for convenience). Ultrasonic washed. It has been found that prolonged ultrasonic cleaning (ie, ultrasonic cleaning for 2 hours or more) can etch the silicon substrate. Therefore, excessive time ultrasonic cleaning in a carbonic acid rinsing solution is avoided in order to prevent the organic monolayer from being removed from the silicon substrate surface by cutting the unprotected edges of the coupon.

  For each acid species listed in Table I used for the preparation of a substrate coated with a monolayer, a coupon having a substrate based on the listed phosphonic acid is bound to the nature of the bond to the substrate surface, the thickness of the layer bonded to the substrate. And analyzed to examine the orientation of the species including the layers. A specially prepared quartz crystal microbalance study was also conducted to determine the packing density of species containing organic monolayers after binding to the surface in parallel (described below).

  In order to investigate the functional groups bound to the substrate in the organic monolayer, a coupon with a dense organic monolayer prepared according to the procedure described above was analyzed by specular reflectance infrared spectroscopy (IR, Reflection from Surface Optics Corp. A Midac Model 2510 spectrophotometer equipped with a rate head) was analyzed according to known procedures. IR analysis performed on each sample confirmed that there was a bond between the oxide functional group on the oxide surface of the substrate and the phosphonic acid functional group of the constituents of the adsorbed monolayer. In order to determine the thickness of the organic layer bonded to the substrate and to investigate the monolayer properties of the organic layer bonded to the substrate, the coupons prepared according to the above procedure were further measured with X-ray reflectometry and atomic force microscopy did.

Atomic Force Microscope Measurement of High Density Organic Monolayer on Silicon Substrate Atomic Force Microscope (AFM) analysis of organic monolayer on substrate is performed using silicon chip (Nanodevices Metrology Probes, resonance frequency: 300 kHz, spring constant: 40 N / m) was performed in a tapping mode using a Digital Instruments Multimode Nanoscope IIIa SPM (Digital Instruments Multimode IIIa SPM).

X-ray reflectivity measurement The X-ray reflectivity measurement was performed with a national synchrotron light source (NSLS) at a wavelength λ = 0.087 nm using a beam line X10b. The measurement was performed in the reflectance mode (Θ to 2Θ), and a momentum shift q _z (q _z = 4π / λ sin Θ) along the surface normal was obtained. A NaI detector was used. The sample slit was set to 0.6 mm and the detector slit was set to 0.8 mm. A rocking scan was performed to check the background level. The incident beam was isolated from materials other than the sample by fixing the sample sideways. Membrane analysis was performed in air. Data was analyzed using a free program based on the Parratt equation (dynamic scattering).

  The AFM and X-ray spectroscopy data for the films prepared in each of Examples 1-3 are shown in Table II below. In the case of α-quaterthiophene-2-phosphonic acid, the surface roughness of the dense organic monolayer deposited on the substrate surface is determined by X-ray analysis to determine the surface of the underlying substrate surface prior to the deposition of the monolayer. It was also confirmed that the roughness was not exceeded. This means that the monolayer of the present invention exhibits a high degree of surface conformation.

  These data in Table II show that monolayers can be formed using the phosphonic acid species of any example, and generally the monolayer is an organic monomolecule that is slightly inclined from the normal to the substrate surface. Represents the orientation of the phosphonic acid species including the layer.

Quartz Crystal Microbalance Packing Density Measurement The density of monolayer species bound to a phosphonic acid-based surface prepared according to the procedure described above is repeated using a quartz crystal microbalance with a silicon electrode instead of a silicon substrate. Measured by. The use of these crystals as model oxide surfaces and in the measurement of crystal mass gain due to surface-bound species has been described by Gawalt et al., Which is incorporated herein by reference in its entirety. , Langmnir 2003, Vol. 19, pp 200-204. The deposition procedure described above was followed using 0.05 mM octadecylphosphonic acid / THF solution or 0.0025 mM α-quaterthiophene-2-phosphonic acid / THF solution. After each processing cycle (adsorption of high density phosphonic acid based monolayer and its binding with oxide surface functional groups), the crystals containing the bound high density phosphonic acid based monolayer are expressed as “Carbonate Rinse”. The solution was rinsed with a flushing stream followed by a stream of deionized water. The crystals were then placed under a vacuum of about 10 mTorr for about 2 hours to evaporate the remaining moisture from the crystals. This rinsing and evaporation cycle was repeated after successive cycles until the crystals exhibited a constant frequency meaning that all multi-layer species had been removed from the surface. Microbalance measurement was performed using the crystals thus prepared. After each microbalance measurement, the crystals were re-cycled until the asymptote reached a mass increase. Table III below shows the density of surface-bound species including a high-density organic monolayer bonded to the oxide surface of the quartz crystal.

  The data in Table III shows that the octadecylphosphonic acid based monolayer has a packing density corresponding to molecular units comprising about 18.5 square angstroms / monolayer. This is approximately in agreement with the value seen in the closely packed crystals of the aliphatic chain of the aliphatic material. The data in Table II also shows that α-quaterthiophene-2-phosphonic acid based monolayers have a packing density corresponding to molecular units comprising about 25.1 square angstroms / monolayer. This is approximately consistent with the value found for crystalline α-quaterthiophene-2-phosphonic acid (23.4 to 25.6 square angstroms / molecular unit). Finally, the data in Table II also shows that 11-hydroxyundecylphosphonic acid based monolayers have a packing density corresponding to about 20.5 square angstroms / molecular unit. This value is equivalent to the value reported as the packing density of the high-density monomolecular layer of octadecylphosphonic acid adsorbed on the mica surface. These data indicate that the monolayer has a dense packing arrangement on the substrate surface. As noted above, the reported packing for sparse monolayer adsorption of octadecylphosphonic acid on mica has not been observed so far for adsorption of octadecylphosphonic acid on surfaces other than mica.

Comparative Example A-Treatment of silicon with bulk α- quaterthiophene-2-phosphonic acid solution A 0.1 mM THF solution of α-quaterthiophene-2-phosphonic acid was prepared as described above. The silicon substrate coupon prepared as described above was immersed in the solution at room temperature for 3 days. The coupon was then removed from the solution and rinsed according to the procedure described above. The rinsed coupon was heated as described above. Formation of the organic layer was not observed.

  100 ml of the α-quaterthiophene-2-phosphonic acid solution prepared as described above was heated to 60 ° C. The silicon substrate coupon prepared as described above was immersed in a heated acid solution for 14 days. After this period, the coupon was removed from the solution according to the procedure described above, dried and heated in an oven. Subsequent analysis of the deposited organic layer by AFM showed that the organic layer contained a multi-layer of phosphonic acid moieties derived from the α-quaterthiophene-2-phosphonic acid used in the preparation.

  The following series of examples illustrates further derivatization of the dense organic monolayers of the present invention based on phosphonic acids having omega functionality.

Example 4-Peptide derivatization of a dense organic monolayer bonded to a silicon substrate This example has a dense organic monolayer based on 11-hydroxyundecylphosphonic acid, following the process of Example 1A above. The silicon substrate was further derivatized by adding biomolecules to the organic layer using terminal hydroxyl functionality present in the component species including the monolayer. The hydroxyl functional group is derivatized by conversion to a maleimide derivative ester (ie, 3-maleimidopropionic acid ester, also referred to herein as “derivative ester” for convenience), and the derivative ester is converted to the tetrapeptide Arg-Gly-Asp-Cys (RGDC). The tetrapeptide bound to the organic monolayer bound to the surface via a thiol ester functional group was obtained. The RGDC peptide used in this example is a fibronectin RGD-containing cell-binding peptide derivatized by adding a cysteine residue at the C-terminus, and is commercially available (American Peptide).

  A series of derivatization reactions leading to conjugated peptides were performed according to the following procedure. A coupon with a dense organic monolayer prepared using 11-hydroxyundecylphosphonic acid prepared according to Example 1A (described above) was prepared under anhydrous conditions using 3-maleimide (propionic acid-N-hydroxysuccini). Mid) ester was placed in 15 mL of a 1 mM acetonitrile solution prepared with thoroughly dried acetonitrile. The solution was kept under anhydrous conditions and the coupon was stirred in the solution for 24 hours at room temperature. The coupon was then removed from the solution under atmospheric conditions and rinsed by sonicating 3 times with acetonitrile in a Branson (R) ultrasonic bath. IR analysis was performed according to the procedure described above and showed that the hydroxyl group at the end of the phosphonic acid moiety containing the organic monolayer attached to the substrate surface was converted to a derivative ester adduct to a considerable extent.

A solution containing 10 mg of the above RGDC peptide was prepared in 15 mL of twice distilled Millipore ™ filtered water and adjusted to pH 6.5 using 0.05 M aqueous NaOH. The coupon containing the organic monolayer having the derivative ester adduct prepared above was placed in the RGDC solution and stirred at room temperature for about 24 hours. The coupon was removed from the solution and rinsed by sonication with double distilled water. The coupon was transferred to a vacuum line and dried under vacuum (about 10 mTorr) for 24 hours. FTIR analysis was performed according to the procedure described above, and it was shown that the mercapto group of the cysteine residue on the RGDC peptide surface formed a thiol ether bond with the derivative ester adduct bound to the organic monolayer. This became clear from the change of the carbonyl region of maleimide derivative ester and the broadening of the carboxylic acid region (˜1700 cm ⁻¹ ). These IR features were found to remain after two solvent rinses, indicating the presence of RGDC tetrapeptide bound to the coupon.

RGDC derivatized silicon coupons prepared as described above were contacted with living cells to determine the ability of the surface to promote cell growth and adhesion to the surface. The following cells were used for contact testing:
(A) Human fetal osteoblasts (HFOB 1.19; ATCC), 1: 1 mixture of Ham F12 and Dulbecco's Modified Eagle Medium (DMEM), phenol red free, (GIBCO, BRL )) 10% fetal calf serum (Hyclone Laboratories), and 0.3 mg / ml G418 Geneticin (Invitrogen);
(B) NIH 3T3 cells cultured in DMEM and 10% calf serum (High Clone Laboratories);
(C) human melanoma cells (A375), human fibrosacroma cells (HT1080) and SV40 transformed human fibroblasts (WI38-VA13) cultured in DMEM and 10% fetal bovine serum; and (d) DMEM, 10% Fetal clone II serum (High clone laboratories), Chinese hamster ovary cells expressing α4 (CHOα4), α5 (CHOα5), or αvB3 integrin cultured in 1% non-essential amino acids and 1 mg / ml geneticin.

Cells were cultured in designated dishes in culture dishes, removed from tissue culture dishes using 2.5% trypsin in 0.2 mg / ml EDTA in PBS and resuspended in complete medium. Approximately 5 × 10 ⁴ cells were added to wells containing Si substrates derivatized with RGDC as described above and blocked with 1% BSA in PBS for 30 minutes. Cells are grown on a derivatized surface for about 1.5 hours, and the number of cells attached to the surface, as well as intracellular organization and adhesion spots of the actin cytoskeleton to stress fibers (actin stress fibers are integrin receptor and extracellular The degree of formation of the protein-rich complex that binds to the substrate was periodically examined with an optical microscope. Organization and proliferation were visualized by staining the adherent cells and tissues with a fluorescent dye and detected using a fluorescence microscope.

  A similar cell adhesion test conducted over 7 days showed continued growth of many cells attached to the substrate modified with the organic monolayer. This indicates the stability of the high-density organic monolayer film on the substrate surface to physiological conditions. Once the cell covering is removed from the modified organic monolayer using the proteolytic enzyme trypsin, the modified organic monolayer can be reused using the procedure described above and new cells can be incubated.

  The following example illustrates that large biomolecules, in this example antibodies, can also be bound to a substrate using the dense organic monolayer provided by the present invention.

Example 5-Antibody Derivatization of a High Density Organic Monolayer Bonded to a Silicon Substrate A substrate having a high density organic monolayer based on 11-hydroxyundecylphosphonic acid prepared according to Example 1A is used to form a coupon. It was derivatized by placing it in a 5 mM acetonitrile solution of luglutarate (DSG, Pierce) for 24 hours at room temperature (about 25 ° C.). The solution was prepared and used under anhydrous conditions (samples were transferred to a nitrogen glove box and acetonitrile was handled from metal sodium using a cannula after distillation). After 24 hours, glutarate derivatized coupons were rinsed with fresh acetonitrile and handled in an inert environment before use.

  Rabbit anti-mouse IgG (Pierce, using commercially available product as it is) binds to glutarate-derivatized monolayer by placing the derivatized coupon in 100 mg / ml phosphate buffer solution (PBS) for 30 minutes at room temperature. It was. After 30 minutes, the reaction was stopped and the coupon was washed with 50 mM Tris-HCl solution (pH 7.4). Coupons in a solution containing anti-α4 integrin antibody P1H4 (Chemicon) or anti-α5 integrin antibody SAM-1 (Cymbus Technology, Ltd.) at a concentration of 10 micrograms / ml. The commercial solution was used as it was.The coupon was removed from the antibody solution, washed with PBS, and blocked with 1% BSA dissolved in PBS for 30 minutes.

  Cells expressing α4 (CHO α4) labeled with Cell Tracker Orange or α5 (CHO α5) labeled with Cell Tracker green are removed from the culture dish using the procedure described above. Cells were prepared previously by treating with each fluorescent label at 37 ° C. for 30 minutes. Using the procedure described above, a mixture of labeled cells was incubated on each antibody derivatized surface. After a contact time of about 2.3 hours, the coupon was visualized with light of the appropriate wavelength. When incubated with cells mixed with α5-derivatized surfaces, to a large extent, only α5-expressing cells grow on the surface, as well as substantially only α4-expressing cells grow on the α4-derivatized surface. It was observed. These observations show that high-density organic monolayers provide a route to prepare specific surfaces for interaction with biomaterials.

  The following group of examples describes the application of the process of the present invention to the application of organic monolayers along a dense surface to the surface of an amorphous planar oxide conductor and to the native oxide surface of a curved metal surface. The use in is illustrated.

Example 6 Deposition of a dense organic monolayer on an indium-doped tin oxide surface A glass substrate with a layer of 125 nm thick tin oxide doped with indium in the conductive state (ITO / glass, Colorado concept A dense organic monolayer was deposited on the conductive oxide surface of Coatings (Colorado Concept Coatings). The substrate was prepared by cutting and breaking the ITO / glass plate to obtain a 100 mm ² coupon. The ITO surface of the coupon was cleaned by ultrasonic cleaning for 30 minutes with 2 wt.% Cleaning solution (Tergitol®) according to the above-described process. After washing with the washing solution, the coupon was rinsed with running deionized water. Each coupon was then boiled for 15 minutes with the respective solvent of methanol, isopropanol, and methylene chloride. The coupon was then dried under anhydrous nitrogen flow and stored under an anhydrous nitrogen blanket until used.

  According to the procedure described above (Example 1) for providing a monolayer film on the silicon substrate surface on the ITO coupon surface prepared as described above, about 0.4 mL of α-quaterthiophene-2-phosphonic acid was added. A dense organic monolayer was deposited using an 0024 mM THF solution through an evaporation step that continued across the ITO coupon surface with an acid solution meniscus for approximately 3 hours. The monolayer film thus prepared was tested by IR spectroscopy and AFM according to the procedure described above. As a result of the test, it was confirmed that the layer deposited on the surface was along the surface, covered substantially the entire surface, and was of a monolayer dimension.

  Even when the ITO coupon prepared as described above was further subjected to ultrasonic cleaning in a 5% by weight THF solution of triethylamine at room temperature (about 1 hour or longer), no change was observed in the organic layer bonded to the surface. This indicates that the organic monomolecular layer is strongly adhered to the ITO surface of the substrate.

Example 7-Deposition of a dense organic monolayer onto a curved metal surface A dense organic monolayer is made of medical grade nickel / titanium alloy (Nitinol®) with a diameter of 6 mm. On the native oxide surface of arterial stents and sections of surgical grade 316 stainless steel 2 mm diameter stents (both stent samples obtained as stock from UTI Corporation Stent Technology Div.) Deposit.

  In preparation for applying a bonded monolayer coat in accordance with the present invention, a nickel / titanium stent was cut into pieces about 15 mm long and a stainless stent was cut into pieces about 17-20 mm long. Prior to deposition, the stent fragments were washed according to the following procedure. The stent is cleaned by ultrasonic cleaning (Branson) for 30 minutes in distilled water solution of Taditol (registered trademark) according to the product instructions, and distilled water (in-house deionized water), methylene chloride (technical grade, commercial products are used as they are. ) By rinsing with ultrasonic washing for 15 minutes each, followed by ultrasonic washing three times for 15 minutes in methanol. After this solution treatment procedure, the stent pieces were dried in an oven at 150 ° C. in air for at least 12 hours.

  3.2 mg of phosphonundecanol (a difunctional phosphonic acid containing a phosphonic acid head group, a terminal alcohol functional group, and a linear alkyl chain of 11 carbon atoms between the two functional groups) immediately before sodium benzophenone A solution dissolved in 20 ml of distilled THF was prepared. The stent was used with the procedure described above for a silicon wafer coupon, except that the stent was submerged vertically in an acid solution and hung with a thin wire threaded through the stent fragment. After coating, the stent pieces were placed in a tube furnace and heated to 125 ° C. for 24 hours. After cooling to room temperature in air, the coated stent pieces were ultrasonically cleaned with fresh methanol for 30 minutes and dried under a vacuum of about 10 Torr for about 12 hours.

  The stent fragment was placed in a 11.6 micromolar acetonitrile solution of Alexafluor-546 carboxylic acid succinimidyl ester® (Molecular Probes) for 24 hours, and Alexafluor with monolayer hydroxyl functional groups By forming the -546 Ester® adduct, the monolayer coated stent fragment prepared as described above was further functionalized. The derivatized stent fragments were rinsed with fresh acetonitrile for 10 minutes by ultrasonic washing and stored under vacuum (approximately 10 Torr) until examined under a fluorescence microscope. Fluorescence microscopic examination of the derivatized stent showed a uniform surface coverage of the fluorescent species. This shows that the process of the present invention can be used to provide a dense organic monolayer even on complex metal shapes.

Claims (37)

  Method for providing a densely oriented bonded monolayer on at least a portion of a substrate having a surface comprising a hydrolyzable functional group onto which a densely oriented monolayer comprising at least one organic acid species is adsorbed And forming a bond comprising at least one of the acid functional groups associated with at least some of the adsorbed organic acid species with one or more of the surface hydrolyzable functional groups.   The method of claim 1, wherein forming the bond comprises heating the substrate and the adsorbed monolayer until at least a portion of the adsorbed monolayer is bonded to the surface of the substrate. (I) providing a substrate surface comprising a plurality of hydrolyzable functional groups;
(Ii) at least one organic acid species having at least one acid functional group on at least a portion of the substrate surface at an interface comprising the adsorbed organic acid species and the surface of the substrate; Adsorbing in an amount sufficient to form a densely oriented monolayer comprising at least some of the acid functional groups in the vicinity of bond formation of hydrolyzable functional groups on the substrate surface; and (iii) the acid functionality Attaching at least a portion of a group at the interface to the hydrolyzable functional group comprising a surface of the substrate;
Providing a densely oriented monolayer on at least a portion of the surface of the substrate.   Repeating steps (ii) and (iii) until the monolayer is substantially free of void areas and covers the entire portion of the substrate surface on which the densely oriented organic monolayer is provided. The method of claim 3, further comprising:   The bonding step (iii) provides sufficient thermal energy at a time sufficient for at least some of the acid functional groups to form chemical bonds with the surface hydrolyzable functional groups at the interface. The method according to claim 3, comprising supplying to the device.   4. The method of claim 3, wherein steps (ii) and (iii) are performed simultaneously.   The adsorbing step (ii) is sufficient to provide a solution containing a low concentration organic acid dissolved in a solvent and to form a monolayer film of the organic acid species on at least a portion of the substrate surface. 4. The method of claim 3, comprising contacting the solution with the substrate surface in an amount.   After contacting the substrate surface with the solution, the residual solution is removed from contact with the substrate under conditions such that the adsorbed densely oriented organic monolayer film is desorbed on at least a portion of the substrate surface. The method of claim 7, further comprising: evaporating any residual solvent from the adsorbed monolayer film, and optionally after or simultaneously with removal of the residual solution.   9. The method of claim 8, wherein removal of the residual solution and evaporation of the residual solvent are performed by traversing a meniscus of acid solution across the substrate surface.   10. The substrate surface traversing the acid solution meniscus is provided by gradually flowing a gas flow toward the interface between the substrate surface and the solution surface on the substrate surface. the method of.   The method according to claim 9, wherein the substrate surface is brought into contact with the solution by suspending the substrate at a fixed position immersed in a large amount of a solution containing organic acid species in a solvent.   The method of claim 11, wherein the substrate surface is traversed by a meniscus of acid solution by evaporating a portion of the solvent from the solution.   The hydrolyzable functional group is an oxide functional group, and the substrate surface has: (a) a material having a native oxide surface with electrically conductive, semiconducting, insulating or metallic properties; and (b) 4. The method of claim 3, comprising an oxide surface of a substrate selected from the group consisting of a bulk oxide, an oxide conductor, and an oxide insulator.   The hydrolyzable functional group is an oxide functional group, and the substrate surface is selected from the group consisting of a metal natural oxide surface, a semiconductor natural oxide surface, an insulator natural oxide surface, and an oxide conductor. 9. The method of claim 8, comprising an oxide surface of the substrate to be processed.   The substrate is a natural surface of a silicon based semiconductor, a bare surface of a silicon based semiconductor, a natural surface of a germanium based semiconductor, a bare surface of a germanium based semiconductor, a natural surface of a gallium arsenide based semiconductor, a gallium arsenide based 9. The method of claim 8, selected from the group consisting of a bare semiconductor surface, an indium tin oxide conductor, an aluminum zinc oxide conductor, a titanium oxide conductor, and an iron oxide conductor.   4. The method of claim 3, wherein the organic acid species has an acid functional group selected from the group consisting of a sulfonic acid functional group, a carboxylic acid functional group, and a phosphonic acid functional group.   9. The optional method of claim 8, wherein the organic acid species is selected from the group consisting of mono-, di-, and polyfunctional carboxylic acids, and mono-, di-, and polyfunctional phosphonic acids.   The organic acid species comprises at least one acid functional group selected from the group consisting of a carboxylic acid functional group and a phosphonic acid functional group, which is linear, branched, or cyclic, saturated or unsaturated, substituted or non- A hydrocarbon moiety selected from the group consisting of a substituted aliphatic moiety, a substituted or unsubstituted aromatic moiety of a monomer, oligomer or polymer, a substituted or unsubstituted monomer, oligomer or polymer heterocyclic aromatic moiety. 9. The method of claim 8, wherein   The hydrocarbon moiety is a substituted or unsubstituted thiophene moiety, a substituted or unsubstituted polythiophene moiety, an oligomeric heterocyclic moiety, a polymeric heterocyclic moiety, a linear or branched, saturated or unsaturated, substituted or unsubstituted An aliphatic moiety having from about 2 to about 40 carbon atoms, a substituted or unsubstituted aromatic or heterocyclic aromatic moiety, a substituted or unsubstituted linear phenylene, an aromatic moiety of a polymer, a TCNQ derivative, And the hydrocarbon moiety is optionally selected from the group consisting of carboxylic acid functional group, hydroxyl functional group, amino functional group, phosphonic acid functional group, ether functional group, polyether functional group, and thiol functional group. The method of claim 18, further substituted with one or more functional groups selected from the group consisting of:   9. The omega-substituted bifunctional carboxylic acid or phosphonic acid, wherein the organic acid species has an omega-substituent selected from the group consisting of hydroxyl, amino, carboxylic acid, phosphonic acid, and thiol functional groups. The method described.   The organic acid species is nitrophenylphosphonic acid, benzylphosphonic acid, butylphosphonic acid, octylphosphonic acid, octadecylphosphonic acid, substituted and unsubstituted anthracenephosphonic acid, substituted and unsubstituted pentacenephosphonic acid, substituted and unsubstituted Quarterthiophenephosphonic acid, 11-hydroxyundecylphosphonic acid, omega-carboxylic acid phosphonic acid having a hydrocarbon moiety containing from about 2 to about 20 carbon atoms, substituted and unsubstituted xylylphosphonic acid, and 2 of these 20. A method according to claim 19 which is a phosphonic acid selected from the group consisting of the above combinations.   The organic acid species from the group consisting of alkyl carboxylic acids having from about 2 to about 40 carbon atoms, benzoic acid, substituents comprising hydroxyl, amino, carboxylic acid functional groups, and optionally hydroxyl, amino, carboxylic acid functional groups Substituted benzoic acid, salicylic acid selected from the group consisting of linear or branched, substituted or unsubstituted, alkyl moieties having from about 2 to about 20 carbon atoms, substituted with one or more selected functional groups And a carboxylic acid selected from the group consisting of substituted and unsubstituted alkylsalicylic acids.   A densely packed organic acid based monolayer chemically bonded to an oxide surface of a substrate prepared according to the method of claim 8.   20. A densely packed organic acid based monolayer chemically bonded to an oxide surface of a substrate prepared according to the method of claim 19.   25. The method of claim 24, further comprising attaching an additional functional group to the organic or bioactive moiety. High density oriented monomolecule using one or more organic acid species containing at least one acid functional group selected from phosphonic acid functional groups and carboxylic acid functional groups on a substrate having a surface containing a plurality of oxide functional groups Here is how to provide a layer:
(I) providing a solution comprising in a solvent at least one said organic acid species comprising at least one said acid functional group, wherein said acid species is present in a low concentration in the solution;
(Ii) at least a portion of the substrate surface on which the monolayer is provided is sufficient to form an adsorbed densely oriented monolayer film comprising organic acid species in the solution obtained in step (i). Contacting at a quantity and under conditions (wherein at the interface between the adsorbed organic acid species and the substrate surface, each adsorbed organic acid species comprising the monolayer comprises at least one oxide functional group on the substrate surface). At least one acid functional group associated with the
(Iii) following the step (ii) of contacting the solution, under conditions where the adsorbed densely oriented monolayer film and optionally the residual amount of the solvent is desorbed on at least a portion of the substrate surface Removing any residual solution from contact with the substrate;
(Iv) after or simultaneously with step (iii) of removing the solution, if present, substantially all of said residual solvent is evaporated; and (v) if step (iv) is performed, step (iv) After or simultaneously with the adsorption of sufficient thermal energy with sufficient duration to form chemical bonds with the oxide functional groups of the substrate surface on at least some of the acid functional groups associated with the oxide surface Supplying an interfacial region comprising a monolayer and the oxide surface;
Including methods.   Repeating steps (i)-(v) until the monolayer is substantially free of void areas and covers the entire portion of the oxide surface on which the monolayer is provided. 27. The method of claim 26.   27. The method of claim 26, wherein the “heating step” (v) comprises placing the substrate in an environment having a temperature greater than about 100 degrees Celsius.   The contacting step (ii) is performed by dispersing a large amount of the organic acid solution on the substrate surface under a condition that at least some of the large amount of solution can form a solution layer on the substrate surface. 30. The method of claim 28.   30. The method of claim 29, wherein the step (iii) of removing the solution is performed according to the method of claim 10.   29. The method of claim 28, wherein the contacting (ii) is performed by suspending the substrate in a fixed position immersed in a volume of the solution.   32. The method of claim 31, wherein the contacting (ii) and removing (iii) are performed according to the method of claim 12.   33. The method of claim 32, wherein the organic acid species is selected from mono-, di-, and polyfunctional phosphonic acids.   The method of claim 32, wherein the organic acid species is selected from mono-, di-, and polyfunctional carboxylic acids.   33. A densely oriented monolayer film provided by the method of claim 32.   33. The method of claim 32, wherein the organic acid species is omega hydroxyalkyl phosphonic acid.   A high density oriented monolayer film prepared by the method of claim 36.